What are the treatment options for Systemic Lupus Erythematosus (SLE)?

Treatment of Systemic Lupus Erythematosus (SLE)

All patients with SLE should receive hydroxychloroquine at a dose not exceeding 5 mg/kg real body weight as the cornerstone of therapy, combined with glucocorticoids and immunosuppressive agents as dictated by disease severity and organ involvement. 1, 2, 3

Foundation Therapy for All Patients

Hydroxychloroquine (Universal Treatment)

• Hydroxychloroquine is FDA-approved for SLE and should be prescribed to all patients unless absolutely contraindicated 3
• Dosing: 200-400 mg daily (not exceeding 5 mg/kg real body weight) 2, 4
• Benefits include reduced disease activity, prevention of flares, and improved survival 2, 5
• Ophthalmological screening is mandatory: baseline examination, repeat after 5 years, then yearly thereafter to monitor for retinal toxicity 2, 4

Adjunctive Measures (All Patients)

• Photoprotection with sunscreens to prevent cutaneous flares 1, 4
• Low-dose aspirin for patients with antiphospholipid antibodies, those receiving corticosteroids, or those with cardiovascular risk factors 1, 4
• Calcium and vitamin D supplementation for patients on long-term glucocorticoids 1

Glucocorticoid Strategy

Acute Disease Management

• Intravenous methylprednisolone pulses provide immediate therapeutic effect for acute flares and enable lower starting doses of oral glucocorticoids 2
• Dosing and route depend on type and severity of organ involvement 2

Chronic Maintenance

• Glucocorticoids must be minimized to less than 7.5 mg/day prednisone equivalent and withdrawn when possible to prevent irreversible organ damage 2, 4, 6
• Prompt initiation of immunomodulatory agents expedites glucocorticoid tapering 4

Organ-Specific Treatment Algorithms

Mild Disease (Mucocutaneous and Musculoskeletal)

First-line:

• Hydroxychloroquine + topical glucocorticoids for skin lesions 4
• NSAIDs for arthritis and pain (with gastroprotection if gastrointestinal risk present) 1, 6

Second-line (if inadequate response):

• Add methotrexate for skin and joint manifestations 2, 4
• Alternatives: azathioprine or mycophenolate mofetil 2

Refractory cases:

• Consider belimumab (FDA-approved for active SLE) 7, 5
• Rituximab for severe refractory disease 2

Lupus Nephritis (Moderate to Severe)

Diagnostic requirement:

• Kidney biopsy is essential before initiating treatment 2

Induction therapy:

• Mycophenolate mofetil OR cyclophosphamide (low-dose preferred over high-dose due to comparable efficacy and lower gonadotoxicity) 2
• High-dose glucocorticoids (intravenous methylprednisolone pulses followed by oral prednisone) 2
• Belimumab is FDA-approved as add-on therapy for lupus nephritis (approved 2020) 7, 5
• Voclosporin (calcineurin inhibitor) is FDA-approved for lupus nephritis 1, 5

Maintenance therapy:

• Mycophenolate mofetil OR azathioprine 2
• Continue hydroxychloroquine 2
• Taper glucocorticoids to lowest effective dose 2

Neuropsychiatric Lupus (NPSLE)

Treatment depends on underlying mechanism:

For inflammatory/immune-mediated mechanisms:

• High-dose glucocorticoids (intravenous methylprednisolone) 1, 2
• Cyclophosphamide (superior to methylprednisolone alone: 18/19 patients responded vs 7/13, p=0.03) 1

For thrombotic/embolic mechanisms:

• Anticoagulation with warfarin 1, 2
• Target INR 2.0-3.0 for first venous thrombosis 1
• Target INR 3.0-4.0 for arterial or recurrent thrombosis 1

For mixed mechanisms:

• Combination of immunosuppressive therapy and anticoagulation 2

Hematological Manifestations

Significant thrombocytopenia:

• Initial therapy: intravenous methylprednisolone pulses 2
• Add immunosuppressive agent: azathioprine, mycophenolate mofetil, or cyclosporine 2
• IVIG for acute phase or inadequate glucocorticoid response 2
• Rituximab or cyclophosphamide for refractory cases 2

Biologic Therapies for Refractory Disease

FDA-Approved Biologics

• Belimumab (anti-BAFF antibody): approved 2011 for active extrarenal SLE, 2020 for lupus nephritis 7, 5
• Anifrolumab (anti-type 1 interferon receptor): approved 2021 for moderate-to-severe extrarenal SLE 1, 5
• Voclosporin: approved 2022 for lupus nephritis 1, 5

Off-Label Biologics

• Rituximab for refractory hematological, cutaneous, or renal manifestations 2, 4

Critical Monitoring and Comorbidity Management

Disease Activity Monitoring

• Use validated activity indices at each visit 1, 4
• Monitor anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment 4

Comorbidity Screening

• SLE patients have 5-fold increased mortality risk 1
• Screen for infections, cardiovascular disease, hypertension, diabetes, dyslipidemia, osteoporosis, and malignancies (especially non-Hodgkin lymphoma) 1, 4
• Consider statins and ACE inhibitors for cardiovascular risk reduction 1

Special Populations

Pregnancy

Safe medications:

• Prednisolone, azathioprine, hydroxychloroquine, low-dose aspirin 1, 4

Contraindicated medications:

• Mycophenolate mofetil, cyclophosphamide, methotrexate 1, 4

Monitoring:

• Patients with lupus nephritis and antiphospholipid antibodies require closer monitoring for preeclampsia 1, 4

Common Pitfalls to Avoid

• Never discontinue hydroxychloroquine without compelling contraindication—non-adherence increases flare rates and mortality 2, 5
• Avoid prolonged high-dose glucocorticoids (>7.5 mg/day) as they cause irreversible organ damage 2, 6
• Do not use NSAIDs without monitoring renal function—lupus nephritis is a risk factor for NSAID-induced acute renal failure 8
• Do not treat based on serological activity alone (rising anti-dsDNA) without clinical correlation—this risks overtreatment 1
• Exclude infections before intensifying immunosuppression—infections are a leading cause of mortality 1